ArticleJournal of medicinal chemistry2006
Topomimetics of amphipathic beta-sheet and helix-forming bactericidal peptides neutralize lipopolysaccharide endotoxins.
Article in Journal of medicinal chemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 54 citations in OpenAlex.
- Defining a lipophilicity window for the antimicrobial activity of 7-Alkoxy-3-Amino coumarin amphiphiles.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Calix[4]API-s: fully functionalized calix[4]arene-based facial active pharmaceutical ingredients.Molecular diversity · 2021Review
- Increasing the Chemical Variety of Small-Molecule-Based TLR4 Modulators: An Overview.Frontiers in immunology · 2020Review
- Norbornane-based cationic antimicrobial peptidomimetics targeting the bacterial membrane.European journal of medicinal chemistry · 2018Article
- What Can Pleiotropic Proteins in Innate Immunity Teach Us about Bioconjugation and Molecular Design?Bioconjugate chemistry · 2018Review
- Usefulness of ELISA Methods for Assessing LPS Interactions with Proteins and Peptides.PloS one · 2016Article
- Calix[4]arene Based Highly Efficient Fluorescent Sensor for Au(3+) and I(.).Journal of fluorescence · 2015Article
- Polycationic calixarene PTX013, a potent cytotoxic agent against tumors and drug resistant cancer.Investigational new drugs · 2013Article
- Bacterial membrane disrupting dodecapeptide SC4 improves survival of mice challenged with Pseudomonas aeruginosa.Biochimica et biophysica acta · 2013Article
- Designed beta-boomerang antiendotoxic and antimicrobial peptides: structures and activities in lipopolysaccharide.The Journal of biological chemistry · 2009Article
- AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense.Trends in immunology · 2009Review
- Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Release of lipopolysaccharide (LPS) endotoxin from Gram negative bacterial membranes triggers macrophages to produce large quantities of cytokines that can lead to septic shock and eventual death. Agents that bind to and neutralize LPS may provide a means to clinically prevent septic shock upon bacterial infection. Previously, we reported the design of antibacterial helix peptide SC4 and beta-sheet-forming betapep peptides that neutralize LPS in vitro. We hypothesized that the ability of these and other such peptides to neutralize LPS rested in the common denominator of positively charged amphipathic structure. Here, we describe the design and synthesis of nonpeptide, calixarene-based helix/sheet topomimetics that mimic the folded conformations of these peptides in their molecular dimensions, amphipathic surface topology, and compositional properties. From a small library of topomimetics, we identified several compounds that neutralize LPS in the 10-8 M range, making them as effective as bactericidal/permeability increasing protein and polymyxin B. In an endotoxemia mouse model, three of the most in vitro effective topomimetics are shown to be at least partially protective against challenges of LPS from different bacterial species. NMR studies provide mechanistic insight by suggesting the site of molecular interaction between topomimetics and the lipid A component of LPS, with binding being mediated by electrostatic and hydrophobic interactions. This research contributes to the development of pharmaceutical agents against endotoxemia and septic shock.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.